Regulatory T cells in elderly patients with asthma.

BACKGROUND: Airway walls in asthma present an accumulation of activated cells that determine bronchial structural changes and disease progression and severity. During the aging process, the immunoinflammatory response changes as a consequence of chronic antigenic stress. OBJECTIVE: To evaluate T-cell subsets with regulatory functions associated with asthma in elderly patients METHODS: A group of 153 individuals (95 with controlled asthma and 58 healthy controls) aged over 65 years was studied. Blood samples were collected for flow cytometry analyses of CD3, CD4, CD8, CD56, CD56CD8, CD3CD4CD25, CD3CD4CD25CD127, CD4HLA-DR and TCRgamma delta. RESULTS: Asthmatic patients showed a statistically significant increase in CD4+ T cells. CD3CD4CD25high and CD3CD4CD25highCD127high cells were also significantly increased in asthmatic patients, while CD3CD4CD25highCD127low cells had similar values in asthmatics and in the control group. CD4HLA-DR cells were within the normal range in both groups. A positive correlation between CD3CD4CD25highCD127low and CD4HLA-DR was observed and gamma delta T cells were significantly decreased in the asthmatic patients compared to the controls. CONCLUSIONS: Since T cells with regulatory functions were within normal ranges or reduced in asthmatic patients compared to healthy controls, at least in basal conditions, it can be speculated that they probably play a limited role in chronic asthma in elderly patients.These data suggest an absence of a modulatory effect on the inflammatory response that characterizes asthma and allergy, which in turn would facilitate the persistence of disease in this population. Underlying inflammatory processes that are involved in chronic diseases associated with aging could provide an additional explanation for the attenuated differences observed between asthmatic and nonasthmatic individuals.

Modulation of endothelial cell inflammatory integrins and stress markers with rh-factor VIIa in patients with advanced chronic hepatitis C.

Individuals with chronic hepatitis C (CHC) progress to cirrhosis and hepatic cancer. Individuals with advanced CHC are coagulopathic and can manifest fibrinolysis. The coagulopathy is a consequence of hepatocytic dysfunction. The fibrinolysis represents a response to local endothelial cell injury, and is of a low-grade. Based upon this hypothesis, the effect of the infusion of recombinant human factor VIIa (rh-FVIIa) on endothelial cell inflammatory integrins and measures of endothelial stress were determined in 17 individuals with advanced CHC. Immediately prior to the infusion of rh-FVIIa, the plasma levels of tissue factor (TF), Thrombomodulin (TM), human soluble ICAM-1 (hs-ICAM-1), human soluble VCAM-1 (hs-VCAM-1), human soluble L-Selectin (hs-L-Selectin), the prothrombin time and the activated partial thromboplastin time were determined. The same parameters were assayed at 5, 10, 30, 120, 240 and 360 min after infusion. TF and TM levels were very high at baseline consistent with a vascular endothelial stress response. Similarly hs-ICAM-1, hs-VCAM-1 as well as L-Selectin levels were increased. Thirty minutes after the infusion, a marked reduction in ICAM-1 and VCAM-1 and to a lesser degree L-Selectin levels was observed. This reduction persisted for 360 min. No change in measures of fibrinolysis [plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (t-TFPI), activated tissue factor pathway inhibitor (TFPIa), d-dimers (DD), FSP and fibrinogen levels] occurred. In addition, no change in plasma Annexin-V was observed. Based upon these data it can be concluded that: (1) rh-FVIIa corrects the coagulopathy seen in advanced CHC; (2) reduces endothelial cell injury and/or stress as evidenced by the TF, TM, hs-ICAM-1 and hs-VCAM-1 levels in plasma; (3) these changes in coagulation occurred without inducing a propagated vascular thrombosis.

A case of localized primary sclerosing cholangitis mimicking intrahepatic bile duct cancer.

A 75-year-old woman with chronic hepatitis was regularly followed-up in our hospital. A computed tomography (CT) scan revealed an obviously enlarged intrahepatic bile duct in the posterior branch of the left lateral segment. Percutaneous cholangiography revealed an enlarged posterior branch of the left lateral segment and a narrow stenotic region at the root of this branch. We diagnosed her as having intrahepatic bile duct cancer, and a left lateral segmentectomy of the liver was performed. However, microscopic examination of the resected specimens revealed peribiliary fibrosis in the stenotic bile duct and other areas of the intrahepatic bile duct with no malignant cells. Thus, the final diagnosis was made to be primary sclerosing cholangitis. We must consider primary sclerosing cholangitis in the differential diagnosis of localized stenosis of the intrahepatic bile duct.

Vascularity of advanced gastric carcinoma: evaluation by using power Doppler imaging.

BACKGROUND: We investigated the vascularity of advanced gastric adenocarcinomas by using percutaneous power Doppler imaging. METHODS: Seventeen patients with gastric cancer and 10 without a gastric tumor, but with a slightly thick gastric wall in the B-mode ultrasound, were investigated with the use of power Doppler imaging. The color signals of the gastric lesion were graded as follows: 1, no color signals or the same as the surroundings; 2, color signals were slightly increasing; and 3, color signals were obviously increasing. RESULTS: The color signals of three patients were graded 1, those of eight patients were graded 2 and those of six patients were graded 3 in the gastric cancer group. The color signals of all 10 patients without a gastric tumor were grade 1. This difference was statistically significant (P = 0.0002). CONCLUSIONS: Power Doppler imaging showed vascularity of gastric cancer increasing in the majority of patients (14 of 17: 82%). Thus, power Doppler imaging might be a good screening examination method for gastric cancer.

Massive rectal bleeding due to ileal tuberculosis.

A patient with massive rectal bleeding due to ileal tuberculosis is reported. Technetium-99m labelled red blood cell scintigraphy indicated hemorrhage from the ileum, and laparotomy was then carried out. A 70-cm segment of ileum containing ulcers and erosions was resected, and epitheloid granuloma with Langhans-type giant cell was found in the resected specimen. Massive rectal bleeding is considered a rare presenting symptom of intestinal tuberculosis. Intestinal tuberculosis, including small intestinal tuberculosis, although uncommon, should be taken into consideration as a cause of rectal bleeding.

Gastric ulcer formation after the Hanshin-Awaji earthquake: a case study of Helicobacter pylori infection and stress-induced gastric ulcers.

BACKGROUND: Both Helicobacter pylori (H. pylori) infection and various stresses are known to induce peptic ulcer disease of the upper gastrointestinal tract. However, the pathogenetic relationship between the two factors has not yet been clarified. We conducted a case-control study to examine whether H. pylori infection played a role in the development of gastric ulcer (GU) induced by life-event stresses that were experienced after the Hanshin-Awaji earthquake. MATERIALS AND METHODS: Serum samples from patients in the devastated area who developed GUs during the 2 months following the Hanshin-Awaji earthquake and those from GU patients in the same area during the corresponding period of the previous year, and from gender-, age- and institute-matched ulcer-free controls were tested for the presence of the H. pylori IgG antibody. RESULTS: A significant association between H. pylori infection and the development of GU in uninjured patients was observed in all sets [matched odds ratio (OR) = 3.23, 95% confidence interval: 1.95-5.35]. Moreover, the prevalence of H. pylori infection in patients who developed GUs after the earthquake was not different from that for GU patients in the previous year. In contrast, there was no association between H. pylori infection and the development of GU in the physically injured patients after the earthquake. CONCLUSIONS: H. pylori infection may play an important role in the development of GUs that are induced by emotional life-event stresses.

Detection of Helicobacter pylori gene by means of immunomagnetic separation-based polymerase chain reaction in feces.

BACKGROUND: Detection of Helicobacter pylori is usually performed by culture, polymerase chain reaction (PCR), histology, or urease test on gastric biopsy samples. Although methods based on feces are non-invasive, their sensitivity has been relatively low. In this study, to improve its sensitivity, immunomagnetic separation (IMS) was used as a pre-PCR step for direct detection of H. pylori in feces. METHODS: Fresh fecal samples were taken from 72 patients attending for endoscopy. Of these, 57 patients had a positive H. pylori status according to the results of culture, histology, and PCR on gastric biopsy samples. Anti-H. pylori antibody-sensitized immunomagnetic beads were used to concentrate the bacteria. PCR was then performed to detect the H. pylori urease A-encoding gene. RESULTS: Of the 57 H. pylori-positive patients, 35 (61.4%) had positive fecal samples by IMS-based PCR method. None of the 15 H. pylori-negative patients had positive fecal samples. The sensitivity of this method was 61.4%, and the specificity 100.0%. CONCLUSIONS: This study confirms that non-invasive diagnosis of H. pylori infection could be made from feces by using IMS-based PCR.

[Results of clinical study with epirubicin hydrochloride injectable solution in hepatoma].

A 10-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with hepatocellular carcinoma. Epirubicin-RTU 60 mg/m2 was injected into the hepatic artery and a three-week drug-free interval followed. Of 15 patients with hepatocellular carcinoma registered in this study, 14 patients were eligible, and they all completed the entire course. The objective was to investigate the safety of treatment with Epirubicin-RTU in 14 eligible patients. The adverse drug reactions frequently observed in these 14 eligible cases were leukopenia, neutropenia, thrombocytopenia, alopecia, and fever. They were all reversible and tolerable. With these results. Epirubicin-RTU was considered to be a safe pharmaceutical product to inject into the hepatic artery.

Peptic ulcers after the Hanshin-Awaji earthquake: increased incidence of bleeding gastric ulcers.

OBJECTIVE: Although physical stresses are known to induce peptic ulcers in the upper gastrointestinal tract, it remains controversial whether emotional stress can cause peptic ulcers. Therefore, we examined retrospectively the influence of the Hanshin-Awaji earthquake that occurred in Japan in January 1995 on the occurrence of peptic ulcer disease among noninjured residents. METHODS: Sixty-one hospitals, covering 70% of all endoscopy examinations performed in this area, joined the study and were divided into three areas according to the severity of the damage. A comparison was made between a group of 10,831 patients who underwent upper gastrointestinal endoscopy within 2 months after the earthquake and 16,100 who did so in the same hospitals during the corresponding period in 1994. RESULTS: In the most devastated area, in spite of a dramatic decrease in the total number of endoscopies (50.0%), patients with gastric ulcer (GU) were increased in 1995, whereas those with duodenal ulcer were decreased, resulting in a higher ratio of gastric to duodenal ulcers than in 1994 (3.07 vs 1.88). In particular, there was a marked increase in bleeding GU. The mean age of patients with GU was significantly higher in 1995 than in 1994. CONCLUSION: The Hanshin-Awaji earthquake-induced life event stress not only triggered but also exacerbated GU, particularly in the elderly.

[Reversal of portal-systemic encephalopathy by shunt-preserving disconnection of portal and systemic circulation].

Obliteration of portal-systemic shunts surgically or by interventional radiological techniques is fairly effective in reversing intractable portal-systemic encephalopathy (PSE), but is often associated with ascites accumulation and/or formation of esophageal varices. This study reports four patients with incapacitating PSE who were treated by interventional radiological techniques via percutaneous transhepatic route. One case had the shunt embolized directly. In the other three the blockage was placed on the proximal part of the splenic vein, whereby disconnecting the mesenteric-portal blood flow from the systemic circulation while preserving the shunt. The patient of shunt closure showed transient correction of encephalopathy, but developed massive ascites and esophageal varices, encephalopathy recurred, resulting in death from hepatic failure two months after the procedure. In the cases of shunt-preserving disconnection of portal and systemic circulation (SPDPS) immediate and permanent clearing of encephalopathy was achieved without manifestation of ascites or esophageal varices during the follow-up period of 10 to 31 months. The difference of portal pressure between before and after the procedure was 18 mmHg in the shunt-closed patient and 3 mmHg in SPDPS group. We conclude from this limited experience that SPDPS can be an effective and safe method in treating PSE in adequately selected patients.

Measurement of functioning hepatocyte mass via [99mTc]galactosyl-neoglycoalbumin.

Technetium-99m-galactosyl-neoglycoalbumin (TcNGA) is a synthetic radiolabeled ligand specific for hepatic binding protein (HBP), a receptor that resides exclusively on hepatocytes. In vivo measurement of receptor concentration was obtained via kinetic analysis of liver and blood time-activity data obtained during the hepatic clearance of intravenously administered TcNGA. The purpose of this study was to assess receptor concentration as a measure of the functioning hepatocyte mass. Therefore, TcNGA and dual-injection indocyanine green maximal removal rate (ICG Rmax) studies were performed on nine patients with hepatic cirrhosis associated or not with hepatocellular carcinoma. Receptor concentration was compared with ICG Rmax, which is a validated method for the estimation of the functioning hepatocyte mass. The correlation coefficient was 0.76 (P = 0.017). It is concluded that HBP concentration ([HPB]o) as measured by functional imaging is a measure of functioning hepatocyte mass. This implies that measurement of an individual's receptor concentration by using nuclear medicine techniques provides an objective index of hepatic functional mass and supports attempts to rigorously evaluate [HBP]o for its clinical efficacy.

Hepatic angiomyolipoma pre-operatively diagnosed by imaging.

An asymptomatic patient with pre-operatively diagnosed solitary angiomyolipoma is reported. The tumour was a well defined, fat density mass on computerized tomography (CT) and magnetic resonance imaging (MRI), and a hyperechoic nodule with a sharp margin on ultrasonography (US). The lesion was hypervascular on arteriography and CT during hepatic angiography. Chemical shift MRI confirmed the fat component within the lesion. Although a review of the literature shows this tumour to be rare and difficult to differentiate from a malignant lesion pre-operatively, the pre-operative diagnosis of angiomyolipoma is considered feasible when the characteristic findings as described here are present.

Quantitative assessment of hepatocellular function through in vivo radioreceptor imaging with technetium 99m galactosyl human serum albumin.

Technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin is a newly developed analog ligand to asialoglycoprotein receptor, which is a hepatic cell surface receptor specific for galactose-terminated glycoproteins. Hepatic functional imaging, which yields estimates of asialoglycoprotein receptor concentration, was performed after intravenous injection of 3 mg technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin. A total of 75 human subjects were studied: 6 controls without liver diseases, 51 patients with chronic liver diseases and 18 patients with acute liver diseases. In chronic liver disease the asialoglycoprotein receptor concentration significantly correlated with the clinical severity based on the criteria of the Liver Cancer Study Group of Japan (rs = -0.890, p = 0.0001). Good correlations between the asialoglycoprotein receptor concentration and conventional liver function tests were also observed. In acute liver disease the asialoglycoprotein receptor concentration correlated well with the normotest (r = 0.796, p = 0.0001), prothrombin time (r = 0.701, p = 0.0002) and total serum bilirubin (r = -0.642, p = 0.0007). We conclude that the parameter, asialoglycoprotein receptor concentration, obtained from the kinetic analysis of technetium 99m diethylenetriaminepentaacetic acid-galactosyl human serum albumin time-activity data, is a sensitive measure of functioning hepatocyte mass in acute and chronic liver disease.

Intrahepatic portosystemic venous shunt: diagnosis by color Doppler imaging.

Intrahepatic portosystemic venous shunt is a rare clinical entity; only 33 such cases have been reported. It may be congenital, or secondary to portal hypertension. Five patients with this disorder are presented, each of whom was diagnosed by color Doppler imaging, including waveform spectral analysis. One patient with clinical evidence of cirrhosis and portal hypertension had episodes of hepatic encephalopathy and elevated blood levels of ammonia. This patient had a large tubular shunt between the posterior branch of the portal vein and the inferior vena cava. Shunts of this type are considered to be collateral pathways which develop in the hepatic parenchyma as a result of portal hypertension. The other four patients had no evidence of liver disease, and all four evidenced an aneurysmal portohepatic venous shunt within the liver parenchyma. Shunts of this type are considered congenital. The diagnosis of intrahepatic portosystemic venous shunts was established by color Doppler imaging, which demonstrated a direct communication of color flow signals between the portal vein and hepatic vein, in addition to the characterization of the Doppler spectrum at each sampling point from a continuous waveform signal (portal vein) to a turbulent signal (aneurysmal cavity), and finally, to a biphasic waveform signal (hepatic vein). As demonstrated by the five patients, color Doppler imaging is useful in the diagnosis of an intrahepatic portosystemic hepatic venous shunt, and the measurement of shunt ratio may be useful in the follow-up and determining the therapeutic option.

Multiple hemangiopericytomas of the spleen.

Splenic tumors are uncommon. Described is a 58-yr-old man with multiple hemangiopericytomas of the spleen. Hemangiopericytoma is categorized as a benign vascular tumor, but has a relatively high malignant potential. A review of the literature shows that the case we present is only the second ever reported of a tumor originating from the spleen. Radiological findings and the treatment of the tumor are discussed.

Receptor index via hepatic asialoglycoprotein receptor imaging: correlation with chronic hepatocellular damage.

Galactosyl human serum albumin is a newly developed receptor-binding agent, specific for the asialoglycoprotein receptor, which resides exclusively on the plasma membrane of mammalian hepatocytes. The receptor-binding agent was synthesized by the covalent coupling of carbohydrate units to human serum albumin. The clinical utility of technetium-99m-labeled galactosyl human serum albumin was evaluated in six control subjects with normal livers and in 50 patients with chronic liver disease. The parameter, receptor index, was derived from liver and heart time-activity data and is the ratio of radioactivity of the liver over the radioactivity of the liver plus the heart at 15 min after the intravenous injection of 3 mg of labeled ligand. Values for the receptor index in the control subjects and in patients with mild, moderate, and severe liver disease were 0.936 +/- 0.015, 0.909 +/- 0.034, 0.848 +/- 0.070, and 0.669 +/- 0.085, respectively. Good correlations were obtained between the receptor index and conventional liver function tests, such as the Child-Turcotte criteria score (rs = -0.776, p = 0.0001), prothrombin time (r = 0.736, p = 0.0001), and the plasma disappearance rate of indocyanine green (r = 0.805, p = 0.0001). These significantly high correlations of the receptor index with classical indicators of hepatic functional reserve suggest that the receptor index is a potentially practical and reliable diagnostic method for estimating the functioning hepatocyte mass and for assessing liver function.